Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lisinopril 5-20 mg once daily was compared with digoxin 0.125-0.375 mg once daily in a double-blind, randomized, parallel-group study involving 217 patients with mild-to-moderate heart failure (New York Heart Association [NYHA] grades II-III) who were maintained on optimized diuretic therapy. After 6 weeks of treatment, digoxin and lisinopril had increased exercise duration by 18 seconds (p = 0.015) and 32 seconds (p = 0.0007), respectively, versus the baseline run-in period. The difference between treatments was not statistically significant (p = 0.1343). After 12 weeks, digoxin and lisinopril had increased exercise duration by 29 seconds and 51 seconds, respectively. The effect of digoxin compared with the baseline value was not significant but that for lisinopril was (p = 0.0027). The difference between treatments approached statistical significance (p = 0.0813). There was no difference between lisinopril and digoxin with regard to their effects on the frequency of ventricular ectopic counts, couplets, or nonsustained ventricular tachycardia. Blood pressures were not significantly different between treatments, although both systolic and diastolic blood pressure were consistently lower in the lisinopril group throughout randomized treatment. The proportions of patients demonstrating an improvement in NYHA grading were similar for both lisinopril and digoxin. Both treatments had similar effects on the symptoms of heart failure. Both drugs appeared to be equally well tolerated with a similar frequency of adverse events reported for both drugs (30% for lisinopril vs 29% for digoxin). Withdrawals from treatment were of a similar frequency for both treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of lisinopril versus digoxin for congestive heart failure during maintenance diuretic therapy. The Lisinopril-Digoxin Study Group. 132 79

A multicenter, randomized, double-blind assessment of 130 patients with congestive heart failure (New York Heart Association functional classes II to IV) was undertaken to assess the therapeutic efficacy of lisinopril, an angiotensin-converting enzyme inhibitor. All the subjects received concurrent therapy with digoxin and diuretics. Assessments performed periodically over 12 weeks revealed that the active treatment was associated with significant improvements in treadmill exercise time, cardiothoracic ratio, ejection fraction, functional status and clinical signs and symptoms of heart failure. Lisinopril exhibited a mild first-dose effect on blood pressure that was not significantly different from that observed with placebo. The incidence of adverse experiences was not markedly different in the 2 study groups, with only mild hypotension and dizziness occurring more frequently in association with the active medication.
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PMID:Comparison of lisinopril versus placebo for congestive heart failure. 253 60

1. The population pharmacokinetics of lisinopril were investigated using data collected from two multicentre trials of lisinopril in the treatment of hypertension in elderly patients (n = 40) and patients with renal disease (n = 20). 2. Lisinopril was started at doses of 2.5-5 mg daily and increased at 2-4 weekly intervals as required for control of blood pressure. Steady-state concentration-time profiles were measured after at least 2 weeks at a constant dose. 3. All concentration-time data were analysed simultaneously using the program NONMEM and the influence of clinical factors on clearance/F and volume of distribution/F was tested. 4. Clearance was significantly influenced by creatinine concentration, age, weight and cardiac failure. No clinical features tested were found to influence volume of distribution. 5. The influence of renal function and cardiac failure on lisinopril clearance has been confirmed using a population pharmacokinetic analysis technique.
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PMID:Lisinopril population pharmacokinetics in elderly and renal disease patients with hypertension. 253 50

The pharmacokinetics of lisinopril were determined in 6 healthy young, 6 healthy elderly and 6 elderly patients with cardiac failure. Lisinopril (5 mg day-1) was administered for 7 days. Plasma lisinopril concentration was measured at 1, 2, 4, 6, 8 and 24 h on days 1 and 7 of the study. The two elderly groups had higher serum lisinopril concentrations than the healthy young subjects (P less than 0.05). There were no significant differences in any of the areas under the curve (AUC) for lisinopril plasma concentration (over time) between the healthy young and healthy elderly groups. The healthy young patients had AUC values on day 7 lower than elderly patients with cardiac failure (P less than 0.01). Creatinine clearance was correlated with lisinopril clearance (r = 0.63; P = 0.006) and with AUC on day 7 (r = -0.67; P = 0.004). Lisinopril clearance was different in the three groups (P less than 0.05): healthy young patients had the highest and elderly patients with cardiac failure the lowest values. Thus, in the elderly a reduced renal clearance of lisinopril leads to higher and more sustained blood levels. In elderly patients with cardiac failure, renal function should be estimated before lisinopril is prescribed as a reduction in dose may be appropriate.
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PMID:Pharmacokinetics of lisinopril (MK521) in healthy young and elderly subjects and in elderly patients with cardiac failure. 289 17

The angiotensin converting enzyme inhibitor, lisinopril, was studied in a cryo-injury model of chronic heart failure. This model is characterized by a progressive decrease in cardiac output starting six weeks after cryo-injury to a 30% decrease in cardiac output 10 weeks after injury. Although histological damage to the myocardial tissue, particularly in the epicardial area, was observed, no significant changes occurred in body weight, mean arterial blood pressure, heart rate or central venous pressure. Daily intraperitoneal injection of 3 mg/kg lisinopril was instituted starting four weeks after injury for a duration of six weeks. Lisinopril completely restored the cardiac output to normal values at the end of this six week period. Thus, converting enzyme inhibition appears to be an effective therapeutic agent in this model of chronic cardiac failure.
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PMID:Effects of lisinopril, a new angiotensin converting enzyme inhibitor in a cryo-injury model of chronic left ventricular failure. 301 31

The effects of angiotensin-converting enzyme (ACE) inhibitors in high-output heart failure have not yet been well established. We evaluated the effects of lisinopril (3 mg/kg/day) on hemodynamics, neurohormones, and survival in 10-week-old spontaneously hypertensive rats (SHR) with aortocaval fistula. Sham-operated treated and untreated SHR served as controls. Cardiac output (CO) was determined by thermodilution method, and renal blood flow (RBF) was assessed by laser-Doppler flowmetry. In sham-operated SHR, 2-week treatment with lisinopril decreased blood pressure (BP), left ventricular (LV) weight, and total peripheral resistance (TPR) (p < 0.01 each) and increased RBF and plasma renin activity (PRA) (both p < 0.05); CO and LV end-diastolic pressure (LVEDP) were unchanged. Fistula creation induced biventricular hypertrophy and high-output heart failure [increased LVEDP, CO, pulse pressure, and plasma norepinephrine (NE) and decreased RBF] with congestive signs (ascites, tachypnea). Lisinopril decreased LVEDP (p < 0.01), increased RBF, prolonged survival (both p < 0.05), and prevented ascites (0 vs. 46%) and increased PRA (p < 0.05) and attenuated the increase in plasma NE. Heart weight, BP, and CO were not affected by lisinopril. Thus, lisinopril ameliorated congestion and improved survival in SHR with fistula without compromising cardiorenal hemodynamics. Venous and renal dilatation and attenuation of vasoconstrictive systems may have contributed to the beneficial effects.
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PMID:Converting enzyme inhibition improves congestion and survival in hypertensive rats with high-output heart failure. 751 28

Lisinopril, a long-acting, angiotensin-converting enzyme inhibitor, was compared with placebo in a randomized, parallel, double-blind, 12-week study of 193 patients with heart failure. All patients were New York Heart Association Functional Class II, III, or IV and had remained symptomatic despite optimal dosing with digoxin and diuretics. After 12 weeks of therapy, the improvement in treadmill exercise duration was greater in the lisinopril group (113 seconds) compared with the placebo group (86 seconds). This improvement in exercise duration was particularly evident in patients with left ventricular ejection fractions less than 35% (lisinopril = 130 seconds; placebo = 94 seconds). In patients receiving lisinopril, the increase in exercise duration was accompanied by an improvement in quality of life as measured by the Yale Scale Dyspnea/Fatigue Index and in signs and symptoms of heart failure. In addition, the lisinopril group had a larger mean increase (3.7%) in left ventricular ejection fraction when compared with the placebo group (1.3%). Thus, lisinopril, administered once daily for 12 weeks, was well tolerated and efficacious in the treatment of heart failure when used concomitantly with diuretics and digoxin.
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PMID:Lisinopril versus placebo in the treatment of heart failure: the Lisinopril Heart Failure Study Group. 756 Feb 47

The prognosis in patients with heart failure (HF) is poor. The angiotensin converting enzyme (ACE) inhibitors are among the most promising of current options, with benefits not only in terms of haemodynamic and clinical improvement but also in mortality. Data are reviewed comparing the once-daily ACE inhibitor lisinopril with captopril or enalapril in patients already receiving digoxin and/or diuretics for heart failure. Data are also reviewed which compare lisinopril with digoxin in patients already receiving diuretics alone for heart failure. Lisinopril is more effective than placebo and at least as effective as captopril or enalapril in these comparative studies on the basis of haemodynamics, exercise test results and clinical signs and symptoms of heart failure. Lisinopril may also be a suitable alternative, as well as being an adjunct, to digoxin in patients already receiving diuretics alone. Lisinopril is usually well tolerated in patients with heart failure. The mechanism of benefit of ACE inhibitors in heart failure is not clear, but apart from blockade of the renin-angiotensin-aldosterone system (RAAS), may also involve modulation of sympathetic stimulation, cardioreparation and regulation of potassium balance. The new ATLAS study (Assessment of Treatment with Lisinopril And Survival) is being conducted to address the question of whether ACE inhibitors in general practice should be given at the current low doses, or at the higher doses used in large survival studies.
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PMID:[Lisinopril in the treatment of heart insufficiency]. 766 80

Angiotensin converting enzyme (ACE) inhibitors are now widely used for the treatment of hypertension and heart failure. They are of particular value in treating hypertensive patients with left ventricular dysfunction, and in diabetics where they have been shown to delay the progression of diabetic nephropathy. Differences in the metabolism, pharmacokinetics, and pharmacodynamics between the various ACE inhibitors generally do not translate into significant clinical differences in the majority of patients. However, fosinopril may be the preferred ACE inhibitor in patients with significant renal dysfunction because of a reduced requirement for dosage reduction. The duration of action of ACE inhibitors is determined by two properties, the plasma half-life and the affinity of binding to tissue ACE. All of the ACE inhibitors (with the possible exception of captopril) can provide satisfactory 24-hour blood pressure control in the majority of patients with mild to moderate hypertension when given once daily. Lisinopril provides consistently better 24-hour control of blood pressure than either captopril or enalapril. Evidence for superior 24-hour blood pressure control over enalapril has not been as well established for the other ACE inhibitors. Captopril may be preferred for initiating therapy in patients with severe heart failure who are at risk of first dose hypertension because of its rapid onset of action and relatively short duration of action. There is evidence, however, that perindopril may have a low risk of first dose hypertension in heart failure because of its gradual onset of action. Long-acting ACE inhibitors may be preferable for chronic therapy of heart failure. All of the ACE inhibitors have a low incidence of adverse effects in both young and elderly patients, and there is no convincing evidence of differences in tolerability between the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Critical assessment of ACE inhibitors. Part 2. 777 72

Treatment with ACE inhibitors has improved the prognosis of cardiac failure (CF). The results of CONSENSUS I, SOLVD and V HEFT II show clinical improvement and longer survival with this therapeutic class of drugs. However, the search for the optimal dosage was not undertaken in these trials (a standard dose was fixed at the onset, average dose of enalapril from 15 to 20 mg/day). In clinical practice, patients are prescribed lower doses of ACE inhibitors (enalapril: 7.5 mg/day) than the averages used in large scale trials. In order to optimise the use of ACE inhibitors, the ATLAS study (Assessment of Treatment with Lisinopril and Survival) was undertaken with the precise objective of comparing two dosages (2.5 to 5 mg/day vs 32.5 to 35 mg/day) of lisinopril on the morbidity and mortality of patients with CF. This international, multicenter, randomised, double-blind parallel group trial aims to include 3,000 patients over 18 years of age with NYHA Classes II, III and IV, and an ejection fraction < or = 30% and to follow them up for 3 to 4.5 years. Nearly 30 French centres will participate in this trial. After an initial, open period of evaluation of tolerance (5 mg to 15 mg/day of lisinopril in France), the patients will be randomised to two groups. After randomisation, all patients will receive 5 mg per day of lisinopril. The "high dose" group will receive 20 mg/day for two weeks, then 30 mg/day in addition to the "open dosage". In cases of intolerance, the dosage may be reduced to 20 mg/day or 10 mg/day, or the drug may be withdrawn.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The ATLAS study (Assessment of Treatment with Lisinopril and Survival); justification and objectives]. 786 22


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